Antioxidants are molecules that work to prevent damage that occurs in cells and body tissues due to both normal bodily processes and exposure to some chemicals. The potential medical benefit of antioxidants may reside in their ability to prevent or slow the oxidation of molecules in the microscopic parts of the body, such as DNA or proteins.

Oxidation is a chemical process in which electrons from a substance are transferred to what is known as an oxidizing agent. Oxidation reactions may produce substances referred to as "free radicals." These molecules may cause chain reactions that can damage many cells in the body. Antioxidants may stop the chain reactions caused by free radicals, and therefore stop the process of this sort of damage occurring in the body. In other cases, antioxidants may stop other kinds of oxidation reactions by becoming oxidized themselves and thus sparing cells and tissues from damage.

The reactions that produce free radicals, called oxidation reactions, are critical for the body to function. However, the cumulative effect of many oxidation reactions may irreversibly damage the body. The human body may require a variety of antioxidants to reduce the impact of the free radicals created by oxidation reactions. If the body has too few antioxidants, then the stress of many oxidation reactions may damage or kill body cells. If enough of these cells are killed or damaged, then illness or disease may result.

Free radicals are considered dangerous because they are atoms with an unstable number of electrons, which makes them more chemically reactive than atoms with a stable number of electrons. These unstable atoms may take electrons from other atoms, such as the ones that make up DNA or proteins. When parts of cells lose electrons, the cell cannot function as well as it should. If affected by free radicals, then DNA may be mutated. Proteins that are affected by free radicals may degrade or unfold. Antioxidants neutralize the electrical charge that free radicals have due to their unstable number of electrons and thus protect body cells and tissues.

While oxygen is considered necessary for life, it may also be the most abundant free radical in the body, because it is highly unstable. The types of oxygen molecules that cause free radicals include hydrogen peroxide and hypochlorous acid. Free radicals created by oxygen include the hydroxyl radical (-OH) and the superoxide anion.

By chelating transition metals, some compounds may contribute to antioxidant defense against free radicals by chelating transition metals. Especially important in this system is the function of iron-binding proteins including transferrin and ferritin to sequester iron.

Antioxidants may be dependent upon one another to prevent oxidation; they may work together to stop free radicals in an quantity that both would not be able to achieve on their own.

Oxidation reactions may occur due to forces outside of the human body. For instance, exposure to tobacco smoke, radiation or environmental contaminants may result in oxidation reactions that damage cells.

Early research on antioxidants investigated their possible use in preventing edible fats from becoming rancid due to oxidation. Vitamins A, C and E were some of the first antioxidants identified by medical science as possibly beneficial to human health.

In addition to being available in a variety of fruits and vegetables, antioxidants are available as supplements. They are one of the most popular categories of supplements available today. Antioxidants are proposed to play a role in preventing many common health disorders, such as Alzheimer's disease, heart disease and some types of cancers. Some experts believe that antioxidants may be a treatment for stroke and medical conditions where the brain slowly loses its ability to function.

There is some debate as to whether consuming antioxidants from foods or in supplement form is actually beneficial to the health of patients. Doctors and other experts do not agree if these chemicals are actually helpful, and clinical trials have not all reached the same conclusion. There is also some concern that consuming too many antioxidants may have negative effects on a person's health. For instance, some experts believe that consuming too much vitamin C may result in kidney stones. However, antioxidants are the subject of increasing research because of the possible role they may play in preventing disease.

Experts are not sure if oxidants cause disease, or if oxidants are produced as a result of the disease. Regardless, the stress caused by oxidants over long periods of time is thought to play a role in the development of many types of diseases, including heart disease, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, some conditions associated with diabetes, and some types of diseases where the brain loses its ability to function properly. The role of free radicals in heart disease is better understood than in other types of diseases. The arteries may harden due to oxidation of bad cholesterol, and over time, this process may result in heart disease.

Measurement of antioxidants is not a straightforward process as this is a diverse group of compounds with different reactivities for different reactive oxygen species. In food science, the oxygen radical absorbance capacity (ORAC) has become the current industry standard for assessing antioxidant strength of whole foods, juices and food additives. Other measurement tests include the Folin-Ciocalteu reagent, and the trolox equivalent antioxidant capacity assay. In medicine, a range of different assays are used to assess the antioxidant capability of blood plasma and of these the ORAC assay may be the most reliable.

The first large randomized trial on antioxidants and cancer risk was the Chinese Cancer Prevention Study, which was published in 1993. This trial investigated the effect of a combination of beta-carotene, vitamin E and selenium on cancer in healthy Chinese men and women at high risk for gastric cancer. The study showed that the combination of beta-carotene, vitamin E and selenium significantly reduced incidence of both gastric cancer and cancer overall.

Another 1994 study, the Beta-Carotene and Retinol (vitamin A) Efficacy Trial (CARET), also demonstrated a possible increase in lung cancer associated with antioxidants.

The 1996 Physicians' Health Study I (PHS) found no change in cancer rates associated with beta-carotene and aspirin taken by U.S. male physicians.

The 1999 Women's Health Study (WHS) tested effects of vitamin E and beta-carotene in the prevention of cancer and cardiovascular disease among women age 45 years or older. Among apparently healthy women, there was no benefit or harm observed from beta-carotene supplementation.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is currently investigating whether taking selenium and/or vitamin E supplements may prevent prostate cancer in men age 50 or older.

The Physicians' Health Study II (PHS II) is a follow up of the earlier clinical trial by the same name and is currently investigating the effects of vitamin E, C and multivitamins on prostate cancer and total cancer incidence.

The term "antioxidants" describes a variety of molecules. The most popularly used antioxidants today are ascorbic acid (vitamin C), glutathione, lipoic acid, carotenes, ?-tocopherol (vitamin E), and ubiquinone (Coenzyme Q10).

Experts have suggested that in order for antioxidants to be possibly beneficial, a person must consume them on a regular basis over a period of many years as the proposed benefits of antioxidants may occur by possibly stopping many oxidation reactions over long periods of time. Therefore, consuming a large number of antioxidant supplements over a day, week or month may not reverse the damage that has already been done by free radicals.

Antioxidants fit into two main classifications: antioxidants created by the body or antioxidants provided by foods that are eaten. Antioxidants that dissolve in water are known as hydrophilic and react with oxidants in the blood and in the free spaces inside cells. Antioxidants that dissolve in fats are known as hydrophobic and help to protect the outer part of the cell, known as the membrane, from a process known as lipid peroxidation. Each type of antioxidant may be more present in some body fluids and tissues than others. For instance, one type of antioxidant may be abundant in the kidneys, but almost absent from the heart while the opposite may be true for another antioxidant. Some antioxidants may occur at about the same concentration in every part of the body.

Antioxidants are found in varying amounts in foods such as vegetables, fruits, grain cereals, legumes, and nuts. Some antioxidants such as lycopene and ascorbic acid can be destroyed by long-term storage or prolonged cooking. Other antioxidant compounds are more stable, such as the polyphenolic antioxidants in foods such as whole-wheat cereals and tea. In general, processed foods are thought to contain less antioxidants than fresh and uncooked foods since preparation processes may expose the food to oxygen.

In order to protect themselves from oxidative stress, living organisms have developed several antioxidant defense systems; many of which depend on minerals for proper functioning. The major enzymatic antioxidant defense systems in the body are: Superoxide Dismutase (SOD), which requires copper, zinc and manganese; glutathione peroxidase, which requires selenium; and catalase, which requires iron.

Although the elements selenium and zinc are sometimes called antioxidant nutrients, they do not actually perform a direct antioxidant action. Instead, the presence of antioxidant nutrients is sometimes necessary for antioxidant enzymes to function correctly.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.